Immunomodulatory ligands targeted to IL-23/Th17 pro-inflammatory axis as novel tools for development of topical drugs for treatment of psoriasis
Public support
Provider
Ministry of Health
Programme
Programme to support medical applied research in 2015 to 2022
Call for proposals
Zdravotnický AV 2 (SMZ0201601)
Main participants
Fakultní nemocnice Královské Vinohrady
Contest type
VS - Public tender
Contract ID
16-27676A
Alternative language
Project name in Czech
Imunomodulační ligandy cílené na prozánětlivou dráhu IL-23/Th17 jako nový nástroj k vývoji zevních antipsoriatických léků
Annotation in Czech
Lupénka, nevyléčitelné chronické autoimunitní onemocnění kůže s výskytem kolem 100 milionů případů světové populace, je úzce spojena s úlohou Th17 buněk. Přeměna nezralých Th0 buněk do vyzrálé populace Th17 je řízena interleukinem 23 (IL-23) sekretovaným aktivovanými dendritickými buňkami ve spolupráci s IL-23 receptorem (IL-23R) zajišťujícím přenos signálu do jádra buňky a následnou produkci a sekreci IL-17A/F, IL-22 a prozánětlivých chemokinů. Nedávno jsme vyvinuli a patentem ochránili novou třídu unikátních vysoce afinních vazebných proteinů, které fungují jako mimetika protilátek a antagonisté IL-23R na primárních lidských T-buňkách. V předkládaném projektu aplikovaného výzkumu chceme prověřit farmakologické parametry jednotlivých forem REX ligandů, otestovat jejich imunosupresivní funkci in vivo na myším modelu indukované lupénky, fúzovat REX varianty s nanovlákny k zevní léčbě a vytvořit bivalentní-bispecifické formy REX ligandů.
Scientific branches
R&D category
AP - Applied research
CEP classification - main branch
FO - Dermatology and venereology
CEP - secondary branch
EC - Immunology
CEP - another secondary branch
EI - Biotechnology and bionics
OECD FORD - equivalent branches <br>(according to the <a href="http://www.vyzkum.cz/storage/att/E6EF7938F0E854BAE520AC119FB22E8D/Prevodnik_oboru_Frascati.pdf">converter</a>)
20801 - Environmental biotechnology<br>20802 - Bioremediation, diagnostic biotechnologies (DNA chips and biosensing devices) in environmental management<br>20803 - Environmental biotechnology related ethics<br>20901 - Industrial biotechnology<br>20902 - Bioprocessing technologies (industrial processes relying on biological agents to drive the process) biocatalysis, fermentation<br>20903 - Bioproducts (products that are manufactured using biological material as feedstock) biomaterials, bioplastics, biofuels, bioderived bulk and fine chemicals, bio-derived novel materials<br>30102 - Immunology<br>30216 - Dermatology and venereal diseases<br>30401 - Health-related biotechnology<br>30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)<br>30403 - Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions [pharmacogenomics, gene-based therapeutics])<br>30404 - Biomaterials (as related to medical implants, devices, sensors)<br>30405 - Medical biotechnology related ethics<br>40401 - Agricultural biotechnology and food biotechnology<br>40402 - GM technology (crops and livestock), livestock cloning, marker assisted selection, diagnostics (DNA chips and biosensing devices for the early/accurate detection of diseases) biomass feedstock production technologies, biopharming<br>40403 - Agricultural biotechnology related ethics
Completed project evaluation
Provider evaluation
U - Uspěl podle zadání (s publikovanými či patentovanými výsledky atd.)
Project results evaluation
During the project, valuable data were obtained on the function of the IL-23 / Th17 pathway and on the potential possibilities of influencing this pathway by small protein blockers called REX ligands. Knowledge has also been gained about the in vivo and in vitro toxicity of these potential drugs for psoriasis, as well as for inflammatory bowel diseases. Some results obtained from mice with an imiquimod-induced psoriasis model indicate a possible therapeutic potential of REX ligands, but the results are very preliminary. The possibility of binding REX molecules to nanofibers was also tested, with some positive results, but these do not yet allow application in practice. It has not been possible to obtain and produce bispecific REX ligands as possible more effective forms of potential drugs. Overall, I rate the project as successfully completed.
Solution timeline
Realization period - beginning
Apr 1, 2016
Realization period - end
Dec 31, 2019
Project status
U - Finished project
Latest support payment
Jun 28, 2018
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP20-MZ0-NV-U/03:1
Data delivery date
Jul 1, 2020
Finance
Total approved costs
11,624 thou. CZK
Public financial support
10,596 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
822 thou. CZK